Modulation of srpx2-mediated angiogenesis

Abstract

The present invention relates to nucleic acids and antibodies against SRPX2 and SRPX2 protein function in angiogenesis. Angiogenesis-related conditions, such as cancer or wound healing, can be treated by the composition comprising the SRPX2 antagonists or agonists, respectively.

Description

[0001]This application claims priority to U.S. provisional Application No. 61 / 034,786 filed on Mar. 7, 2008, the entire disclosure of which is specifically incorporated herein by reference in its entirety without disclaimer.BACKGROUND OF THE INVENTION[0002]I. Field of the Invention[0003]The present invention relates generally to the fields of molecular biology and oncology. More particularly, it concerns compositions comprising an inhibitory nucleic acid or an antibody for SRPX2, a novel angiogenesis modulator, or an SRPX2 polypeptide, and associated methods of treating angiogenesis-related conditions.[0004]II. Description of Related Art[0005]Angiogenesis is a multi-step cellular process of capillary sprouting and formation of neo-vasculature from preexisting blood vessels. The complex process involves disassembly of endothelial junctions, followed by endothelial cell detachment, proliferation and migration as well as subsequent re-establishment of intercellular and cell-matrix cont...

AI Technical Summary

Benefits of technology

[0018]The invention is also directed in certain embodiments to a pharmaceutical composition comprising one or more of the nucleic acids, or the antibody or the fragment thereof, and a pharmaceutically acceptable carrier. In certain aspects, the composition may be administered to a cell expressing urokinase-type plasminogen activator receptor (uPAR), since SRPX2 may be a ligand for uPAR to effect the angiogenic activity. The composition may optionally further comprise a lipid component, which is believed to likely give the nucleic acid an improved stability, efficacy and bioavailability, with perhaps even reduced toxicity. The lipid component may form a liposome, but this is not believed to be required. In certain aspects, the composition further comprises cholesterol or polyethyleneglycol (PEG).

Problems solved by technology

Angiogenesis-related diseases result when the angiogenic process is disregulated, resulting in excessive amounts of new blood vessels or an insufficient number of blood vessels.

Retinal neovascularization occurs in ischemic retinopathies such as diabetic retinopathy and is a major cause of visual loss in working age patients (Klein et al., 1984).

Choroidal neovascularization occurs as a complication of age-related macular degeneration and is a major cause of visual loss in elderly patients (Ferris et al., 1984).

However, it was less successful with other tumors for which alternate factors may be involved.

On the other hand, insufficient angiogenesis is also related to a large number of diseases and conditions, such as cardiovascular diseases (e.g., coronary artery diseases) and delayed wound healing.

These treatment modalities have significant limitations in individuals with diffuse atherosclerotic disease or severe small vessel coronary artery disease, in diabetic patients, as well as in individuals who have already undergone surgical or percutaneous procedures.

Although such studies demonstrated proof of concept, additional studies raise issues that still have not been resolved, such as the duration of exposure of the vessels to angiogenic factors and the brief half-lives of such proteins.

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